title: Hyperglycemia attenuates myocardial preconditioning of remifentanil.
abstract: BACKGROUND
  Hyperglycemia attenuates cardioprotection by remifentanil-preconditioning in ischemia-reperfusion in vivo in diabetic rats. However, the effects of hyperglycemia in cultured ventricular myocytes remains unknown. Therefore, we examined the in vitro effects of hyperglycemia on hypoxia-reoxygenation (H/R) and cardioprotection from remifentanil-preconditioning in isolated neonatal rat ventricular myocytes (NRVMs), including effects on apoptotic signaling pathways and Ca(2+) homeostasis.
  
  
  METHODS
  NRVMs were cultured in medium with 5.5 mM (normoglycemia) or 25.5 mM glucose for one day. Then, NRVMs in H/R groups were exposed to 1 h of hypoxia and 5 h of reoxygenation with or without remifentanil-preconditioning at 1 μM. Cell viability, apoptosis, and Ca(2+) homeostasis were assessed by MTT assay, caspase-3 assay, confocal microscopy and immunoblots.
  
  
  RESULTS
  In normoglycemia, remifentanil-preconditioning improved the viability of cardiomyocytes (P < 0.01) and prevented the increase of caspase-3 activity and Ca(2+) overload after H/R injury (P < 0.05). In addition, decrease in Akt, ERK1/2, and Bcl-2, and the increase in Bax by H/R was attenuated by remifentanil-preconditioning (P < 0.05). However, in hyperglycemia, the viability was partially impaired after H/R but not improved by remifentanil-preconditioning. Apoptotic activity, Ca(2+) concentration, and apoptotic kinases except Akt were not affected by either H/R or remifentanil-preconditioning under hyperglycemia. Akt phosphorylation was decreased by H/R but not restored by remifentanil preconditioning.
  
  
  CONCLUSIONS
  Remifentanil preconditioning under normoglycemia renders NRVMs resistant to H/R injury by reducing apoptosis and intracellular Ca(2+) concentrations. The mechanism appears to be modulation of apoptotic signaling. However, hyperglycemia mitigates H/R injury in NRVMs, and may reduce the protective effect of remifentanil-preconditioning that may be associated with the Akt pathways.
authors.affiliation: Department of Life Science, College of Natural Sciences, Ewha Women's University, Seoul, Republic of Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Young Lan
authors.initials: YL
authors.lastname: Kwak
authors.forename: Ki Chul
authors.initials: KC
authors.lastname: Hwang
authors.forename: Yon Hee
authors.initials: YH
authors.lastname: Shim
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D000860:Hypoxia / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D000077208:Remifentanil; D002118:Calcium